Students must be able to interpret, relate, and incorporate new information with existing knowledge and apply the new information to solve novel problems. Peer instruction is a cooperative learning technique that promotes critical thinking, problem solving, and decision-making skills. Therefore, we tested the hypothesis that peer instruction enhances meaningful learning or transfer, defined as the student’s ability to solve novel problems or the ability to extend what has been learned in one context to new contexts. To test this hypothesis, our undergraduate exercise physiology class of 38 students was randomly divided into two groups: group A (n = 19) and group B (n = 19). A randomized crossover design in which students either answered questions individually or during peer instruction was used to control for time and order effects. The first factor that influences meaningful learning is the degree of mastery of the original material. Importantly, peer instruction significantly enhanced mastery of the original material. Furthermore, the student’s ability to solve novel problems was significantly enhanced following peer instruction. Thus pausing two to three times during a 50-min class to allow peer instruction enhanced the mastery of the original material and enhanced meaningful learning, i.e., the student’s ability to solve novel problems.